1. Field of the Invention
The present application discloses embodiments which relate to the field of analyte concentration measurement, more specifically, glucose concentration measurement, and, in some embodiments, algorithms and methods of temperature and/or pH correction, and measurement devices which perform temperature and/or pH correction.
2. Description of the Related Art
Types 1 and 2 diabetes are endocrine disorders characterized by abnormalities in the body's ability to regulate glucose metabolism. While the underlying pathology of these two illnesses differ, both are associated with significant complications including diabetic nephropathy, neuropathy, retinopathy, problems with wound healing, as well as an elevated risk of cerebrovascular and cardiovascular disease. While the mechanism of action is uncertain, it is believed that elevated glucose levels are associated with the release of various inflammatory mediators that produce vascular damage ultimately leading to these complications. Abnormally low glucose levels can also be problematic resulting in anxiety, weakness, and in extreme cases coma and death. Researchers and clinicians have increasingly become aware of the importance of maintaining tight control of glucose levels, particularly in acute care settings, so as to prevent these complications from occurring and to facilitate patient recovery.
While clinicians have used insulin for decades to regulate glucose levels in diabetics, determining precise dosages remains a problem. Insulin has the overall effect of reducing circulating glucose levels through a series of complex interactions involving a number of hormones and cell types. While dosage protocols for insulin attempt to replicate the physiologic secretion of the hormone by the pancreas, administering according to fixed times and algorithms based on serum glucose measurements can only crudely approximate the ability of a healthy individual to continuously adjust insulin production in response to glucose levels and the needs of the body. It follows that in order to determine the precise amount of insulin that must be administered to maintain a patient's circulating glucose levels at a normal level, it is necessary to have an extremely accurate measurement of how much glucose is present and available to the patient at any given time.
Unfortunately, existing methods of determining a patient's glucose level leave much to be desired. Clinicians and diabetic patients routinely test glucose levels by testing unprocessed blood. While the results can be available quickly, they can often be inaccurate. Glucose freely diffuses in and out of red blood cells which can cause the result to vary depending on the concentration of such cells in the sample. Furthermore, the diffusion of glucose out of blood cells is often magnified by the requirement that the whole blood be diluted, thus altering the osmotic potential across the membranes of the blood cells.
A more accurate determination of the patient's glucose level can be obtained by measuring plasma glucose. This requires the separation of the plasma from the other components of the blood such as red and white blood cells. There exist a number of analytical methods for measuring plasma glucose concentration. These include the measurement of the current produced by glucose oxidation, the use of the hexokinase reaction, or through the use of mass spectrometry. While the latter represents the “gold standard” for glucose measurement, these methods can be technically complicated, time-consuming, and are frequently not cost-effective for clinical use. For example, for the most accurate readings, lipids should be removed from the plasma and the results should be adjusted for the sodium content, but both are rarely done. Finally, the results can vary depending on how much protein-bound and intercellular glucose has been released into the sample prior to and during processing. While plasma glucose measurements can provide relatively accurate information, transportation and processing times can lead to a significant delay between when the sample is collected and when the results are available to the clinician. Therefore, it is not feasible to use plasma glucose measurements for near-instantaneous, or “real-time” monitoring of a patient's glucose level.